Cognitive dysfunction in systemic lupus erythematosus is associated with disease activity and oxidative stress: a comparative study with rheumatoid arthritis for identifying biomarkers

Abstract

Background The prevalence and pathophysiological mechanisms of cognitive deficits (CD) Systemic Lupus Erythematosus (SLE) and Rheumatoid arthritis (RA) are very heterogeneous and poorly understood. We characterized CD in patients with SLE compared with RA patients and healthy controls. We compared the neuropsychological profile of SLE and RA with patients’ oxidative/inflammatory biomarkers for CD. Methods We performed a cross-sectional study, including 50 SLE patients, 29 RA patients, and 32 healthy controls. SLEDAI and DAS28 assessed disease activity. SF-36 questionnaire and a battery of cognitive tests were applied to all participants. Blood samples were collected to determine IL-6, S100ß, myeloperoxidase (MPO), malondialdehyde and reduced glutathione (GSH) alterations. Results In the SLE group, higher GSH was associated with the absence of CD (With CD = 69 ± 49, Without CD = 112 ± 81, p = 0.030), while higher IL-6 was associated with the presence of CD in the RA group (With CD = 603 ± 173, Without CD = 431 ± 162, p = 0.032). Regarding specific cognitive domains, in SLE higher MPO was associated with poor performance in reasoning and abstraction (p = 0.039), higher IL-6 was associated with poor performance in inhibitory control and attention (p = 0.031), and higher GSH was associated with better performance in memory(p = 0.021). Higher SLEDAI was associated with poor performance in semantic fluency(p = 0.031), inhibitory control, and attention in the SLE group(p = 0.037). In the RA group, higher DAS-28 was associated with poor performance in executive functions(p = 0.016) and phonemic fluency (p = 0.003). Conclusion SLE patients’ disease activity, inflammatory state, and oxidative stress were associated with CD. In RA patients, CD was associated with disease activity and inflammatory state. These results encourage further studies with larger samples aiming to confirm oxidative stress parameters as biomarkers of CD in SLE patients.